Fish Oil Increases Bile Acid Synthesis in Male Patients with Hypertriglyceridemia

• Published in: The Journal of nutrition Vol. 136; no. 4; pp. 987 - 991
• Main Authors: Jonkers, Iris J. A. M, Smelt, Augustinus H. M, Princen, Hans M. G, Kuipers, Folkert, Romijn, Johannes A, Boverhof, Renze, Masclee, Ad A. M, Stellaard, Frans
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.04.2006; American Society for Nutritional Sciences
• Subjects: bezafibrate; Bezafibrate - adverse effects; Bezafibrate - therapeutic use; bile acids; Bile Acids and Salts - biosynthesis; Biological and medical sciences; Blood Glucose - analysis; blood lipids; Body Mass Index; Chenodeoxycholic Acid - biosynthesis; cholesterol; Cholesterol - biosynthesis; Cholic Acid - biosynthesis; Clofibric Acid - adverse effects; Cross-Over Studies; dietary supplements; drug evaluation; drug therapy; Fasting; Feeding. Feeding behavior; fish oils; Fish Oils - administration & dosage; Fundamental and applied biological sciences. Psychology; Gallstones - chemically induced; human diseases; human nutrition; Humans; hypertriglyceridemia; Hypertriglyceridemia - drug therapy; Hypertriglyceridemia - metabolism; Insulin - blood; Insulin Resistance; lipid metabolism; Lipids - blood; Male; men; Middle Aged; nutritional intervention; Triglycerides - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; bezafibrate; Nutrition; Metabolic diseases; Lipids; Male; Hyperlipoproteinemia; Biosynthesis; Lipoprotein; triglycerides; Edible oil; Triglyceride; bile acid synthesis; Enzymopathy; Fish oil; Hypertriglyceridemia; Bile acid; Dyslipemia
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1093/jn/136.4.987

Fibrates are drugs of choice in patients with hypertriglyceridemia (HTG), but may increase the risk for gallstones by decreasing bile acid synthesis. Fish oil might be a therapeutic alternative, but its effect on bile acid metabolism in humans is unknown. We compared the effects of triglyceride-lowering therapy by fish oil or bezafibrate on cholesterol synthesis and bile acid metabolism in HTG. Cholesterol synthesis, bile acid pool sizes, and synthesis rates were compared between 9 male HTG patients and 10 normolipidemic controls matched for age, sex, and BMI. Effects of bezafibrate or fish oil were studied only in HTG patients in a randomized crossover trial. Patients had 14-fold higher serum triglyceride concentrations and greater cholesterol synthesis, as indicated by a 107% higher ratio of serum lathosterol to cholesterol (P < 0.01) than controls. The groups did not differ in bile acid metabolism. Both bezafibrate and fish oil reduced serum TG concentration (-68 and -51% vs. baseline, respectively). Compared with baseline, bezafibrate therapy was associated with reduced cholesterol synthesis (-25%, P = 0.009) without changes in bile acid synthesis rate and pool size. In contrast, fish oil increased bile acid synthesis (+31% vs. baseline, P = 0.07 and +53% vs. bezafibrate, P = 0.02) and altered bile acid distribution, as reflected by an increased ratio of the cholic acid (CA) synthesis rate to the chenodeoxycholic acid (CDCA) synthesis rate (+35% vs baseline, P = 0.05 and + 32% vs bezafibrate, P = 0.07) without effects on bile acid pool size or cholesterol synthesis. In conclusion, cholesterol synthesis is greater in HTG patients than in controls, whereas bile acid synthesis does not differ. Bezafibrate and fish oil have similar triglyceride-lowering capacities, but distinct effects on cholesterol synthesis. Bile acid synthesis is increased by fish oil, but not by bezafibrate therapy.